Project Summary/Abstract This proposal addresses a critical gap in the research regarding a major public health issue ? use of electronic cigarettes (ECs) by smokers. Smokers cite reducing perceived harm from smoking as a leading reason for using ECs, and ECs have been suggested by tobacco researchers as a potential harm reduction vehicle for smokers who cannot or will not achieve smoking cessation. However, current knowledge of the toxicology of ECs is primarily limited to lab tests, with very little corresponding evidence in behavioral studies. As the first human behavioral EC study in which toxicant exposure via the tobacco-specific nitrosamine, NNAL, a highly potent pulmonary carcinogen will be measured, this project will address a critical barrier in the field and advance science on the widely used practice of EC use for harm reduction. Furthermore, this will be the first study to determine how uptake of ECs affects cognitive-perceptual factors involved in sustained tobacco use, such as risk perceptions, utility of smoking, self-efficacy to quit, and tobacco dependence. This study is directly relevant to the NIH?s mission to address cancer risk factors and supports the long-term objective to reduce the disease burden of tobacco use. In the current proposal, cigarette smokers who are not planning to quit smoking, express interest in harm reduction, and who have never been regular EC users (< 25 times in life) will be randomized in a 2:1 fashion to an EC group (n=120) or an assessment-only control group (n=60). Those randomized to EC will receive a 12 week supply of a second generation EC starter kit with their choice of liquid flavor from a standard list. Those randomized to assessment only (n=60) will not be provided with EC. Tobacco consumption in both groups will be assessed at weeks 0 (baseline), 4, 8, and 12. Changes in toxic exposure (NNAL, a primary lung carcinogen and the primary outcome) and carbon monoxide (CO) will be measured from baseline to week 12. Aim 1 will characterize the toxic exposure of cigarette smokers randomized to the EC group compared to cigarette smokers randomized to assessment-only controls; Aim 2 will assess the effects of uptake of e-cigarettes on perceptions of harm and utility of products; Aim 3 will illuminate patterns of tobacco product consumption (cotinine-verified) among smokers switching to electronic cigarettes and identify baseline predictors of those patterns, including demographic, smoking history, and psychosocial characteristics. This project will advance science on the widely used practice of EC use for harm reduction by being the first known study in which toxicant exposure via NNAL and change in cognitive-perceptual variables among smokers switching to EC will be characterized and compared to smokers who continue to use cigarettes alone. Study findings will have major public health implications, particularly for smokers who have experienced difficulty in quitting cigarettes and for whom EC use as a harm reduction strategy has been considered. The study will enhance the research environment at the PI?s university which is classified as both a Hispanic Serving Institution and an Asian American-Native American-Pacific Islander Serving Institution.